Accelerated elimination from the circulation of homologous aged red blood cells in rats bearing anti-spectrin antibodies

In order to analyse a possible role of anti-spectrin antibodies in the clearance of aged red blood cells (RBC), a homologous system was employed, whereby a population of aged RBC, obtained by hypertransfusion, was injected into rats bearing a high level of anti-spectrin antibodies, following immunization with spectrin. The aged RBC bound the anti-spectrin antibodies 'in vitro' and were eliminated from circulation in spectrin-treated rats at a faster rate than in control rats with naturally occurring antibodies. The analysis of the clearance curves revealed aged RBC of heterogeneous lifespans: two principal populations of short- and longer-living could be identified. In rats with anti-spectrin antibodies, the survival of the short-living population was further reduced. However, the similar kinetics of elimination of aged RBC in the two groups (with naturally-occurring and induced antibodies, respectively) suggest that anti-spectrin antibodies strengthened the intervention of the naturally-occurring ones. On the basis of these results, we assume that during their aging in circulation, RBC can accumulate surface alterations to make spectrin accessible to antibodies so that, in addition to anti-band 3 antibodies, anti-spectrin antibodies may contribute to their elimination.     

Über das regelmässige Vorkommen von Lipoproteiden im Harn des Gesunden

Journal of Molecular Medicine - Der Urin des Gesunden enthält regelmäßig kleine Mengen Eiweiß, die mit den üblichen Eiweißproben nicht nachweisbar sind. Es setzt sich,...     

Treatment of mice with the anticoccidial drug Toltrazuril does not interfere with the development of a specific cellular intestinal immune response to Eimeria falciformis

Immunity against Eimeria-infections is highly specific and it depends on cell-mediated effector mechanisms. Infections of BALB/c mice with 1000 sporulated oocysts of Eimeria falciformis led to protection against challenge infections. Treatment with the anticoccidium Toltrazuril, during primary infection, terminated the ongoing disease and did not interfere with the establishment of protective immunity against challenge infections. Mesenteric lymph node cells of infected, treated as well as non-treated and challenged BALB/c mice, showed a similar proliferation upon stimulation with parasite antigen. In contrast, neither cells of the Peyers patches, intraepithelial lymphocytes, nor spleen cells responded to stimulation with parasite antigens. Cells from all compartments and of all investigated groups proliferated and released the cytokines IFN- and IL-4 in response to the mitogen Concanavalin A. The number of cells releasing IFN- or IL-4 was not dependent on the status of infection or previous treatment with Toltrazuril. The serum IgG response against total sporozoite antigens of individual mice showed that in addition, a systemic humoral response developed in infected mice, independent of a previous drug treatment, although the specific IgG antibody concentration was higher in non-treated mice. Thus, Toltrazuril does not impair the parasite specific intestinal cellular and systemic antibody response and does not prevent the development of protection against challenge infection.     

Prenatal diagnosis of intrauterine rubella

Summary The results of prenatal diagnosis of fetal rubella infection by specific IgM antibody detection in fetal blood obtained in the 21st to 23rd weeks of pregnancy of women with different types of rubella problems during pregnancy (categorised in four groups) showed that in 28 of 31 cases the diagnosis apparently assisted in the correct management of the pregnancy. However, in two cases with negative IgM findings in the fetal blood, children with rubella embryopathy were born, and in one case with positive IgM antibody findings, the child was infected but healthy. From this experience we recommend that in all cases of symptomatic rubella infection in the first 12 weeks, termination of pregnancy should be considered without prenatal diagnosis. Prenatal diagnosis, if considered at all, should be limited to symptomless acute rubella infection and reinfection in the first 12 weeks and to symptomatic rubella infection in the 12th to 17th weeks of pregnancy.

---

Pränatale Diagnose der intrauterinen Rötelninfektion

Zusammenfassung Ergebnisse der pränatalen Diagnose der fetalen Rötelninfektion durch Nachweis von spezifischen Röteln-IgM-Antikörpern im fetalen Blut, entnommen in der 21. bis 23. Schwangerschaftswoche von Frauen mit unterschiedlichen Rötelnproblemen in der Schwangerschaft, eingeteilt in vier Gruppen, zeigen, daß in 28 der 31 Fälle die Diagnose zur richtigen Maßnahme geführt hat. In zwei Fällen jedoch mit negativem IgM-Antikörperbefund im fetalen Blut wurden Kinder mit Rötelnembryopathie geboren, und in einem Fall mit positivem Antikörperbefund war das Kind zwar infiziert, doch bei der Geburt und später gesund. Aufgrund unserer Erfahrung empfehlen wir bei allen Fällen mit symptomatischer und serologisch gesicherter akuter Rötelninfektion und auch Rötelnreinfektion in den ersten 12 Schwangerschaftswochen die Interruptio ohne vorherige pränatale Diagnose. Die pränatale Diagnostik sollte, falls gewünscht, auf symptomlose, serologisch verdächtige Rötelninfektion und Reinfektion in den ersten 12 Wochen und auf symptomatische Infektion ab der 12. bis 17. Schwangerschaftswoche beschränkt werden.

     

Oral session 1 — Multiple sclerosis (1)

Oral Sessions

Oral session 1 — Multiple sclerosis (1)     

Excretion of modified nucleosides during development of malignant lymphomas in mice after whode body irradiation

Summary During x-ray-induced development of malignant lymphomas in mice their urinary excretion of eight modified nucleosides was monitored and the values were compared to the results of the histological examination of the animals at time of their sacrifice.It was found that the pathologically augmented excretion of modified nucleosides begins as much as several weeks before the malignant lymphomas can be diagnosed clinically. Thus some mice had increased levels of modified nucleosides even 10 weeks before sacrifice, though at the time of sacrifice the histological investigation reveled only some small foci of reticulum cell neoplasm in their spleen.It is therefore stressed that the usefulness of the determination of urinary modified nucleosides as an early noninvasive screening test for cancer in man and as an in vivo carcinogenicity test should be evaluated.Abbreviations pseudouridine - m¹A 1-methyladenosine - m⁵C 5-methylcytidine - m¹I 1-methylinosine - m¹G 1-methylguanosine - m²G N ²-methylguanosine - m²G N ²,N²-dimethylguanosine - ac⁴C N ⁴-acetylcytidine - mt⁶A N-(9--d-ribofuranosylpurine-6-yl)N-methylcarbamoyl) threonine - acp³U 3-(3-amino-3-carboxypropyl) uridine - SD standard deviation     

Chromosomal instability rather than p53 mutation is associated with response to neoadjuvant cisplatin-based chemotherapy in gastric carcinoma.

PURPOSE: The objective of the study was to evaluate microsatellite alterations [microsatellite instability (MSI) and loss of heterozygosity (LOH)] and mutation in the p53 gene in relation to response and patient survival to a cisplatin-based neoadjuvant chemotherapy in gastric cancer. EXPERIMENTAL DESIGN: Fifty-three pretherapeutic gastric carcinoma biopsies were analyzed with 11 microsatellite markers. The entire coding region of the p53 gene (exons 2-11) was analyzed for mutations by denaturing high-pressure liquid chromatography and sequencing. p53 protein expression was evaluated by immunohistochemistry. Patients were treated with a cisplatin-based, neoadjuvant chemotherapy regimen. Therapy response was evaluated by computed tomography scan, endoscopy, and endoluminal ultrasound. The median follow-up of the patients was 45.6 months. RESULTS: p53 mutations were identified in 19 of the 53 (36%) analyzed tumors. No significant association with response or survival was found for p53 mutation or for p53 protein expression. MSI (either high-grade MSI or low-grade MSI) did not show a correlation with response. With respect to LOH, LOH at chromosome 17p13 showed a significant association with therapy response (P = 0.022) but did not reach statistical significance in terms of patient survival. The global LOH rate, expressed as fractional allelic loss (FAL), was assessed, and tumors were classified into tumors with a high (>0.5), medium (>0.25-0.5), and low (0-0.25) FAL value. A statistically significant association of FAL with therapy response was found (P = 0.003), with a high FAL being related to therapy response. The sensitivity, specificity, positive predictive value, and negative predictive value for FAL > 0.5 were 45%, 93%, 82%, and 72%, respectively. CONCLUSIONS: A high level of chromosomal instability (high FAL value) defines a subset of patients who are more likely to benefit from cisplatin-based neoadjuvant chemotherapy. p53 mutation status is not significantly associated with therapy response and is not a useful marker for response prediction.     

Letal verlaufende Varizellen nach Nierentransplantation

Zusammenfassung Wir berichten über ein 7 Jahre altes M?dchen, das 14 Tage nach einer Nierentransplantation an Varizellen erkrankte. Erste Symptome waren krampfartige Bauchschmerzen mit radiologischen Hinweisen auf einen Obturationssubileus bei Obstipation. Als nach abführenden Ma?nahmen keine Besserung auftrat, wurde eine Probelaparotomie mit Entfernung des Tenckhoff-Dialysekatheters durchgeführt. Dabei zeigte sich kein pathologischer Befund, insbesondere fanden sich keine Briden. Zwei Tage nach Beginn der abdominalen Symptomatik trat ein zun?chst uncharakteristisches Exanthem auf. Aus den sich in den n?chsten 12 h entwickelnden Bl?schen konnte Varicella-Zoster-Virus isoliert werden. Trotz hochdosierter Gabe von Aciclovir und Varicella-Zoster-Immunglobulin entwickelte sich ein fulminantes Leberversagen mit Verbrauchskoagulopathie. Die Patientin verstarb am 18. postoperativen Tag trotz intensiver supportiver Therapie im Multiorganversagen. Diskussion: Vor dem Hintergrund dieser letalen Varizelleninfektion wird auf die Komplikationen und die teilweise untypischen Verl?ufe von Windpocken bei immunsupprimierten Kindern hingewiesen. Eine aktive Impfung ist daher bei seronegativen Patienten vor einer geplanten Organtransplantation zu fordern.      

Mycotoxin Exposure in Children through Breakfast Cereal Consumption in Chile

Mycotoxins are unavoidable contaminants produced by fungi in food, especially grains. This study aimed to measure the occurrence and levels of total aflatoxins (AFs); ochratoxin A (OTA); zearalenone (ZEN); fumonisins B1, B2, and B3 (FUM); deoxynivalenol (DON); and T-2/HT-2 toxins in the four most commonly consumed breakfast cereals in Chile and to assess mycotoxin exposure and risk in children aged 2 to 13 years due to cereal consumption. In this study, a total of 110 batches with three subsamples of the four brands were sampled in supermarkets from November 2019 to June 2021. Samples were analyzed by Veratox^® ELISA (Neogen). Exposure was assessed by estimated daily intake (EDI) considering the levels found in a modified lower bound (mLB) and upper bound (UB). Risk was estimated by margin of exposure (MOE) in the case of OTA and AFs and hazard quotient (HQ) for the rest of the mycotoxins. No T2/HT2 toxins were detected. Few samples had quantifiable levels of ZEN, FUM, and DON except for brand 1, with a mean (standard deviation, SD) of 54 (20), 1552 (351), and 706 (218) ng/g, respectively. In addition, three FUM samples and one DON sample had values over the Chilean regulation. Brands 2, 3, and 4 had quantifiable levels of AFs, with mean (SD) values of 1.3 (0.1), 2.1 (0.6), and 1.9 (0.4) ng/g, respectively. Brand 3 had quantifiable levels of OTA, with a mean (SD) of 2.3 (0.4) ng/g. Estimated exposure indicated a risk of AFs in all scenarios, and of FUM for brand 1 consumption, OTA and DON for brand 3 consumption, and OTA for brand 4 consumption in the mLB worst-case scenario. In general, mycotoxin levels were below the Chilean regulatory limits, but most of them were above the EU regulation for processed cereal-based food in young children. Because the risk was higher in the 2- to 5-year-old children, we recommend special regulations for this group in Chile.